title: Exenatide once weekly versus daily basal insulin as add-on treatment to metformin with or without a sulfonylurea: a retrospective pooled analysis in patients with poor glycemic control.
abstract: Basal insulin (b-INS) is typically the add-on treatment of choice for patients with poor glycemic control (ie, glycated hemoglobin [HbA1c] level ≥ 8.5%), but it is unclear whether b-INS is the best option. In this post hoc analysis, the efficacy and tolerability of exenatide once weekly (EQW) were compared with those of b-INS in patients with type 2 diabetes mellitus and a baseline HbA1c level 8.5% who were undergoing treatment with metformin ± a sulfonylurea. Data were pooled from two 26-week, randomized, controlled trials (EQW vs insulin glargine and EQW vs insulin detemir [EQW, N = 137; b-INS, N = 126]). Treatment with either EQW or b-INS for 26 weeks was associated with significant improvements in HbA1c level compared with baseline, although patients treated with EQW experienced a significantly greater decrease in HbA1c level than those treated with b-INS (least squares [LS] mean ± SE: -2.0% ± 0.08% vs -1.6% ± 0.08%; P = 0.0008). Treatment with EQW was associated with a weight loss of 2.4 kg ± 0.23 kg (LS mean ± SE), whereas treatment with b-INS was associated with a weight gain of 2.0 kg ± 0.24 kg (LS mean difference between groups, -4.4 kg ± 0.33; P < 0.0001). Patients in the EQW group were significantly more likely to achieve the composite endpoint of an HbA1c level < 7.0%, no weight gain, and no hypoglycemic events (defined as a blood glucose level < 54 mg/dL requiring self-treatment or assistance to resolve) than patients in the b-INS group (33.6% vs 3.2%; P < 0.0001). The exposure-adjusted hypoglycemic event rates were 0.08 and 0.37 events per patient-year in the EQW and b-INS groups, respectively. Gastrointestinal adverse events occurred at a higher rate in patients who underwent EQW treatment than those who were treated with b-INS. These results show that EQW treatment was associated with significantly greater improvement in HbA1c level compared with b-INS treatment among patients with poor glycemic control, with the added benefits of weight loss (vs weight gain with b-INS therapy) and a lower incidence of hypoglycemic events. These results suggest that EQW is an alternative treatment to b-INS for patients with type 2 diabetes mellitus and a baseline HbA1c level ≥ 8.5%.
authors.affiliation: Amylin Pharmaceuticals, LLC, San Diego, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Steven C
authors.initials: SC
authors.lastname: Brunell
authors.forename: Erich
authors.initials: E
authors.lastname: Blase
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage*; D012189:Retrospective Studies; D014688:Venoms / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D010455:Peptides; D014688:Venoms; D008687:Metformin; D000077270:Exenatide